Paolo Sassone-Corsi

Paolo Sassone-Corsi (8 June 1956 – 22 July 2020) was an Italian molecular biologist, epigeneticist, and researcher. He is known for his contributions in the areas of transcriptional regulation, epigenetics, circadian biology, and metabolic regulation. Together with his brother Emilio Sassone-Corsi, they founded the Neapolitan Astronomy Club (Gruppo Astrofili Napoletani) His passions grew from astronomy to biology, and eventually genetics.

Beginning in 2006, he worked for the University of California, Irvine as a professor and head of chair of the pharmacology department. In 2011, he founded and directed the Center of Epigenetics and Metabolism.

During the course of his life, Sassone-Corsi has published multiple books. In 2013, he published a book of reflections titled "Ti sembra il Caso?: Schermaglia fra un narratore e un biologo", written alongside Erri De Luca. He also wrote another book with Erri De Luca Through the study of signal transduction mechanisms, he investigated how they modulate nuclear functions such as gene expression, chromatin remodeling, and epigenetic control.

Early research on transcription

During his time as a postdoc, working under the mentorship of Pierre Chambon at IGBCM in 1980, Sassone-Corsi studied transcriptional elements and identified the promoter sequence of the adenovirus major late gene, which later became known as the TATA box. Later, Sassone-Corsi moved to the Salk Institute for Biological Studies and made important advancements in understanding the transcriptional autoregulation of the proto-oncogene, fos. Oncogenes which encode for nuclear proteins include, fos, jun, and p53, just to name a few. As a nuclear oncogene, fos is able to initiate cell growth, differentiation, and development which can cause cancer if over-induced. The c-fos protein contains a "leucine zipper" that allows it to form a heterodimer with jun, another oncogene.

Circadian biology research

In 2006, Sassoni-Corsi illuminated the role of chromatin remodeling in circadian mechanisms through the discovery that CLOCK acts as a histone acetyltransferase (HAT) by recruiting P300 and CBP, allowing it to help restore rhythmicity in Clock mutants. This activity allows CLOCK to control the acetylation of BMAL1 and H3. This was important in demonstrating the role of chromatin remodeling in the core clock mechanism and revealed new associations between cellular physiology and histone acetylation. He later helped discover that the histone deacetylase (HDAC) activity of SIRT1, which is NAD+ dependent, undergoes circadian regulation, counteracts the HAT activity of CLOCK, and has in vivo circadian control. In 2009, Sassone-Corsi also helped discover that NAMPT, a rate-limiting step involved in NAD+ salvaging, has circadian expression regulated by CLOCK:BMAL1. His research found that NAMPT was essential to altering the circadian expression of genes; in the same study, he discovered a transcriptional-enzymatic feedback loop between circadian rhythms and cellular metabolism which was an impactful contribution to investigating the links between the two.

Signaling pathways

Sassone-Corsi was influential in investigating the role of chromatin in signaling with a study he conducted in 2000. He revealed that signaling pathways act directly on chromatin components to regulate certain processes; N-terminal tails of histones are acted upon with reversible covalent modifications to elicit responses in multiple pathways. They investigated the interactions that occur when multiple modifications are present on the N-terminal tails at the same time and proposed that H2B-H3 and H2A-H4 are the tails which act as signaling platforms. His research segued into a broader understanding of the role histone modifications play in the complex circuitries of gene regulation. He identified that EGF stimulation activates the MAP kinase pathway which leads to sequential modifications of chromatin.

Honors and awards Philips European Award for Young Investigators (1977) Member of the European Molecular Biology Organization (1990) Medal of the European Molecular Biology Organization (1994) Rosen Prize (Fondation de la Recherche Médicale), France (1996) Prix Liliane-Bettencourt (1997) Segerfalk Award Lecture, Lund University, Sweden (2001) ISI Highly Cited (2003) Grand Prix Charles-Leopold Mayer of the French Academy of Sciences (2003) Edwin B. Astwood Award Lecture of The Endocrine Society, USA (2004) The Umesono Memorial Award Lecture, The Salk Institute, San Diego, USA (2004) Silver Medal of the French National Centre for Scientific Research (2004) Athalie Clarke Achievement Award, University of California, School of Medicine (2010) Roy O. Greep Award Lecture, 2011, Laureate Award by The Endocrine Society (2011) The Ipsen Award in Endocrinology, France (2011) External Member, Max Planck Society, Germany (2011) Transatlantic Medal of The Society for Endocrinology, UK (2012) Dr. Henry Friesen Plenary Lecture Award, Canada (2013) Fellow, American Association for the Advacement of Science, USA (2014) August and Marie Krogh Medal, Denmark (2015) Leonardo da Vinci Gold Medal, FMSI Federation, Rome, Italy (2016) Albert Hogan Memorial Award Lecture, University of Missouri (2017) Distinguished Faculty Award for Research, University of California, Irvine (2019)

Books Sassone-Corsi, Paolo(editor); T.Fuller, Margaret; Braun, Robert.,(2011), Germ Cells. Cold Spring Harbor Laboratory Press, ISBN 9781936113514 Sassone-Corsi, Paolo; Christen, Yves.,(2012), Epigenetics, Brain and Behavior. Springer, ISBN 9783642279126 Sassone-Corsi, Paolo; De Luca, Erri.,(2013), Ti sembra il caso?: Schermaglia fra un narratore e un biologo (Is that right?: Skirmish between a writer and a biologist). Feltrinelli Editore, ISBN 9788807491436 Sassone-Corsi, Paolo; De Luca, Erri; Valin, Daniele.,(2016), Le cas du Hasard: Escarmouches entre un écrivain et un biologiste (The case of change: Skirmish between a writer and a biologist). Galimard, ISBN 9782070179275 Sassone-Corsi, Paolo; Christen, Yves.,(2017), A Time for Metabolism and Hormones. Springer, ISBN 9783319270685 Sassone-Corsi, Paolo(editor); Young, Michael(editor), B.Reddy, Akhilesh.,(2018), Circadian Rhythms. Cold Spring Harbor Laboratory Press, ISBN 9781621821243